Genetics Doesn't Help Predict Diabetes Risk

January 21, 2010

Genetics Doesn't Help Predict Diabetes Risk

A comparative study shows that lifestyle factors are more effective.

A couple of years ago, spurred by a strong family history of
diabetes and journalistic curiosity, I took one of the newly available
genetic tests to asses my risk for the disease. The test assessed whether I carried a
variant called TCF7L2, which was discovered by
scientists at deCode in 2005–almost 20 percent of people with type 2 diabetes
carry two copies of the high-risk version of the gene.

Since then, scientists have discovered a number of other
genetic risk factors for type 2 diabetes, and tests to detect them are
available directly to consumers via the internet, along with an analysis of
that person’s lifetime risk. But a new study confirms what some have said all
along–that these analyses add little to our ability to predict who will get the
disease. So-called phenotypic factors, such as age, body mass index, waist circumference, and cholesterol levels are much more accurate predictors.

Risk of developing type 2 diabetes is highly dependent on
environmental factors, notably diet and obesity. But it also has a strong genetic
component–someone with a sibling with the disease is much more likely to get it
than someone without, regardless of diet. Companies including 23andMe and
Navigenics have marketed genetic tests to assess risk of type 2 diabetes and
other diseases with the idea that this information can help people try to
prevent diseases for which they are genetically at risk. But the new study
calls that into question.

Researchers from the University
College London followed thousands of individuals in London’s Whitehall district
over roughly 20 years. When they looked specifically at factors affecting type
2 diabetes risk, they found that two non-genetic risk models were better
predictors of diabetes risk than a genetic model based on nearly two dozen risk
alleles.

…When the researchers assessed the
so-called Cambridge and Framingham type 2 diabetes risk models, which are based
on non-genetic factors such as age, sex, family history, waist circumference,
body mass index, smoking behavior, cholesterol levels and so on, they found that
both predicted risk of the disease better than a genetic risk model based on 20
common, independently inherited risk SNPs.

The Cambridge model had 19.7 percent
sensitivity for detecting type 2 diabetes cases in the Whitehall cohort based
on a five percent false positive rate, while the Framingham model had 30.6
percent sensitivity. The gene count score, meanwhile, detected 6.5 percent of
cases at a five percent false positive rate and 9.9 percent of cases at a 10
percent false positive rate. In addition, the team noted, adding genetic risk
information did not significantly improve the ability to identify individuals
at risk of type 2 diabetes over either non-genetic risk model alone.

The researchers who conducted the
study didn’t discount studies searching for genetic risk factors for diabetes.
They said that the most useful outcome of those studies will be a better
understanding of the biological basis of the disease, potentially pointing
toward new drug targets.

Direct-to-consumer genomics
companies say it’s too soon to disregard the value to the individual. It’s not
yet clear whether people will be more motivated by a genetic risk than an
environmental one. Or whether the ability to intervene very early on, as
genetic risk factors would allow, is more effective than later interventions.

Here’s 23andMe’s response, via GenomeWeb:

Joanna Mountain, senior director of
research for direct-to-consumer genetics firm 23andMe, agreed that non-genetic
factors are important contributors to type 2 diabetes risk. But she says there
is still a place for genetic testing–particularly for a subset of individuals
with a relatively high genetic risk for the disease.

“One point that the authors
don’t make is that a small fraction of individuals learn from genetic data that
their type 2 diabetes risk is very high,” Mountain told GWDN by
e-mail. “The results for these individuals don’t influence the statistic
that is used heavily in this study, but for those individuals, the genetic
information can be very valuable.”

Mountain also noted that genetic
testing allows for earlier risk assessment than non-genetic factors. And, she
said, in contrast to weight, body mass index, and other non-genetic factors,
genetic profiles do not change over time.

23andMe currently evaluates eight of
the 20 alleles tested in the study. Mountain said the company will continue
adding genetic markers for type 2 diabetes risk as these alleles meet their
scientific criteria.